SLC45A3 Serves as a Potential Therapeutic Biomarker to Attenuate White Matter Injury After Intracerebral Hemorrhage

Abstract

AbstractIntracerebral hemorrhage (ICH) is a severe cerebrovascular disease, which impairs patients’ white matter even after timely clinical interventions. Indicated by studies in the past decade, ICH-induced white matter injury (WMI) is closely related to neurological deficits; however, its underlying mechanism and pertinent treatment are yet insufficient. We gathered two datasets (GSE24265 and GSE125512), and by taking an intersection among interesting genes identified by weighted gene co-expression networks analysis, we determined target genes after differentially expressing genes in two datasets. Additional single-cell RNA-seq analysis (GSE167593) helped locate the gene in cell types. Furthermore, we established ICH mice models induced by autologous blood or collagenase. Basic medical experiments and diffusion tensor imaging were applied to verify the function of target genes in WMI after ICH. Through intersection and enrichment analysis, gene SLC45A3 was identified as the target one, which plays a key role in the regulation of oligodendrocyte differentiation involving in fatty acid metabolic process, etc. after ICH, and single-cell RNA-seq analysis also shows that it mainly locates in oligodendrocytes. Further experiments verified overexpression of SLC45A3 ameliorated brain injury after ICH. Therefore, SLC45A3 might serve as a candidate therapeutic biomarker for ICH-induced WMI, and overexpression of it may be a potential approach for injury attenuation. Graphical Abstract